Simon Rosenbaum

Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis

Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The primary aim of this systematic review and meta‐analysis was to assess the prevalence of MetS and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder, comparing subjects with different disorders and taking into account demographic variables and psychotropic medication use. The secondary aim was to compare the MetS prevalence in persons with any of the selected disorders versus matched general population controls. The pooled MetS prevalence in people with severe mental illness was 32.6% (95% CI: 30.8%‐34.4%; N = 198; n = 52,678). Relative risk meta‐analyses established that there was no significant difference in MetS prevalence in studies directly comparing schizophrenia versus bipolar disorder, and in those directly comparing bipolar disorder versus major depressive disorder. Only two studies directly compared people with schizophrenia and major depressive disorder, precluding meta‐analytic calculations. Older age and a higher body mass index were significant moderators in the final demographic regression model (z = −3.6, p = 0.0003, r2 = 0.19). People treated with all individual antipsychotic medications had a significantly (p<0.001) higher MetS risk compared to antipsychotic‐naïve participants. MetS risk was significantly higher with clozapine and olanzapine (except vs. clozapine) than other antipsychotics, and significantly lower with aripiprazole than other antipsychotics (except vs. amisulpride). Compared with matched general population controls, people with severe mental illness had a significantly increased risk for MetS (RR = 1.58; 95% CI: 1.35‐1.86; p<0.001) and all its components, except for hypertension (p = 0.07). These data suggest that the risk for MetS is similarly elevated in the diagnostic subgroups of severe mental illness. Routine screening and multidisciplinary management of medical and behavioral conditions is needed in these patients. Risks of individual antipsychotics should be considered when making treatment choices.

Physical activity interventions for people with mental illness: a systematic review and meta-analysis

OBJECTIVE To determine effects of physical activity on depressive symptoms (primary objective), symptoms of schizophrenia, anthropometric measures, aerobic capacity, and quality of life (secondary objectives) in people with mental illness and explore between-study heterogeneity. DATA SOURCES MEDLINE, Cochrane Controlled Trials Register, PsycINFO, CINAHL, Embase, and the Physiotherapy Evidence Database (PEDro) were searched from earliest record to 2013. STUDY SELECTION Randomized controlled trials of adults with a DSM-IV-TR, ICD-10, or clinician-confirmed diagnosis of a mental illness other than dysthymia or eating disorders were selected. Interventions included exercise programs, exercise counseling, lifestyle interventions, tai chi, or physical yoga. Study methodological quality and intervention compliance with American College of Sports Medicine (ACSM) guidelines were also assessed. DATA EXTRACTION AND ANALYSIS Two investigators extracted data. Data were pooled using random-effects meta-analysis. Meta-regression was used to examine sources of between-study heterogeneity. RESULTS Thirty-nine eligible trials were identified. The primary meta-analysis found a large effect of physical activity on depressive symptoms (n = 20; standardized mean difference (SMD) = 0.80). The effect size in trial interventions that met ACSM guidelines for aerobic exercise did not differ significantly from those that did not meet these guidelines. The effect for trials with higher methodological quality was smaller than that observed for trials with lower methodological quality (SMD = 0.39 vs 1.35); however, the difference was not statistically significant. A large effect was found for schizophrenia symptoms (SMD = 1.0), a small effect was found for anthropometry (SMD = 0.24), and moderate effects were found for aerobic capacity (SMD = 0.63) and quality of life (SMD = 0.64). CONCLUSIONS Physical activity reduced depressive symptoms in people with mental illness. Larger effects were seen in studies of poorer methodological quality. Physical activity reduced symptoms of schizophrenia and improved anthropometric measures, aerobic capacity, and quality of life among people with mental illness. TRIAL REGISTRATION PROSPERO registration #CRD42012002012.

Exercise as a treatment for depression: A meta-analysis adjusting for publication bias

The effects of exercise on depression have been a source of contentious debate. Meta-analyses have demonstrated a range of effect sizes. Both inclusion criteria and heterogeneity may influence the effect sizes reported. The extent and influence of publication bias is also unknown. Randomized controlled trials (RCTs) were identified from a recent Cochrane review and searches of major electronic databases from 01/2013 to 08/2015. We included RCTs of exercise interventions in people with depression (including those with a diagnosis of major depressive disorder (MDD) or ratings on depressive symptoms), comparing exercise versus control conditions. A random effects meta-analysis calculating the standardized mean difference (SMD, 95% confidence interval; CI), meta-regressions, trim and fill and fail-safe n analyses were conducted. Twenty-five RCTs were included comparing exercise versus control comparison groups, including 9 examining participants with MDD. Overall, exercise had a large and significant effect on depression (SMD adjusted for publication bias = 1.11 (95% CI 0.79-1.43)) with a fail-safe number of 1057. Most adjusted analyses suggested publication bias led to an underestimated SMD. Larger effects were found for interventions in MDD, utilising aerobic exercise, at moderate and vigorous intensities, in a supervised and unsupervised format. In MDD, larger effects were found for moderate intensity, aerobic exercise, and interventions supervised by exercise professionals. Exercise has a large and significant antidepressant effect in people with depression (including MDD). Previous meta-analyses may have underestimated the benefits of exercise due to publication bias. Our data strongly support the claim that exercise is an evidence-based treatment for depression.

Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: a systematic review and large scale meta-analysis

Type 2 diabetes mellitus (T2DM) is highly predictive of cardiovascular diseases and can have particularly deleterious health impacts in people with severe mental illness (SMI), i.e. schizophrenia, bipolar disorder or major depressive disorder. This meta‐analysis aimed: a) to describe pooled frequencies of T2DM in people with SMI; b) to analyze the influence of demographic, illness and treatment variables as well as T2DM assessment methods; and c) to describe T2DM prevalence in studies directly comparing persons with each specific SMI diagnosis to general population samples. The trim and fill adjusted pooled T2DM prevalence among 438,245 people with SMI was 11.3% (95% CI: 10.0%‐12.6%). In antipsychotic‐naïve participants, the prevalence of T2DM was 2.9% (95% CI: 1.7%‐4.8%). There were no significant diagnostic subgroup differences. A comparative meta‐analysis established that multi‐episode persons with SMI (N=133,470) were significantly more likely to have T2DM than matched controls (N=5,622,664): relative risk, RR=1.85, 95% CI: 1.45‐2.37, p<0.001. The T2DM prevalence was consistently elevated in each of the three major diagnostic subgroups compared to matched controls. Higher T2DM prevalences were observed in women with SMI compared to men (RR=1.43, 95% CI: 1.20‐1.69, p<0.001). Multi‐episode (versus first‐episode) status was the only significant predictor for T2DM in a multivariable meta‐regression analysis (r2=0.52, p<0.001). The T2DM prevalence was higher in patients prescribed antipsychotics, except for aripriprazole and amisulpride. Routine screening and multidisciplinary management of T2DM is needed. T2DM risks of individual antipsychotic medications should be considered when making treatment choices.

How much physical activity do people with schizophrenia engage in? A systematic review, comparative meta-analysis and meta-regression

OBJECTIVE Physical activity (PA) improves health outcomes in people with schizophrenia. It is unclear how much PA people with schizophrenia undertake and what influences PA participation. We conducted a meta-analysis to investigate PA levels and predictors in people with schizophrenia. METHOD Major databases were searched from inception till 02/2016 for articles measuring PA (self-report questionnaire (SRQ) or objective measure (e.g. accelerometer)) in people with schizophrenia, including first episode psychosis (FEP). A random effects meta-analysis and meta-regression analysis were conducted. RESULTS 35 studies representing 3453 individuals with schizophrenia (40.0years; 64.0% male) were included. Engagement in light PA was 80.44min (95% CI 68.32-92.52, n=2658), 47.1min moderate-vigorous PA (95% CI 31.5-62.8, n=559) and 1.05min (95% CI 0.48-1.62, n=2533) vigorous PA per day. People with schizophrenia engaged in significantly less moderate (hedges g=-0.45, 95% CI -0.79 to -0.1, p=0.01) and vigorous PA (g=-0.4, 95% CI -0.60 to -0.18) versus controls. Higher light to moderate, but lower vigorous PA levels were observed in outpatients and in studies utilizing objective measures versus SRQ. 56.6% (95% CI 45.8-66.8, studies=12) met the recommended 150min of moderate physical activity per week. Depressive symptoms and older age were associated with less vigorous PA in meta-regression analyses. CONCLUSIONS Our data confirm that people with schizophrenia engage in significantly less moderate and vigorous PA versus controls. Interventions aiming to increase PA, regardless of intensity are indicated for people with schizophrenia, while specifically increasing moderate-vigorous PA should be a priority given the established health benefits.

Dropout from exercise randomized controlled trials among people with depression: A meta-analysis and meta regression.

OBJECTIVE Exercise has established efficacy in improving depressive symptoms. Dropouts from randomized controlled trials (RCTs) pose a threat to the validity of this evidence base, with dropout rates varying across studies. We conducted a systematic review and meta-analysis to investigate the prevalence and predictors of dropout rates among adults with depression participating in exercise RCTs. METHOD Three authors identified RCTs from a recent Cochrane review and conducted updated searches of major electronic databases from 01/2013 to 08/2015. We included RCTs of exercise interventions in people with depression (including major depressive disorder (MDD) and depressive symptoms) that reported dropout rates. A random effects meta-analysis and meta regression were conducted. RESULTS Overall, 40 RCTs were included reporting dropout rates across 52 exercise interventions including 1720 people with depression (49.1 years (range=19-76 years), 72% female (range=0-100)). The trim and fill adjusted prevalence of dropout across all studies was 18.1% (95%CI=15.0-21.8%) and 17.2% (95%CI=13.5-21.7, N=31) in MDD only. In MDD participants, higher baseline depressive symptoms (β=0.0409, 95%CI=0.0809-0.0009, P=0.04) predicted greater dropout, whilst supervised interventions delivered by physiotherapists (β=-1.2029, 95%CI=-2.0967 to -0.3091, p=0.008) and exercise physiologists (β=-1.3396, 95%CI=-2.4478 to -0.2313, p=0.01) predicted lower dropout. A comparative meta-analysis (N=29) established dropout was lower in exercise than control conditions (OR=0.642, 95%CI=0.43-0.95, p=0.02). CONCLUSIONS Exercise is well tolerated by people with depression and drop out in RCTs is lower than control conditions. Thus, exercise is a feasible treatment, in particular when delivered by healthcare professionals with specific training in exercise prescription.

Evaluating an individualized lifestyle and life skills intervention to prevent antipsychotic‐induced weight gain in first‐episode psychosis

AIM Initiating antipsychotic medication frequently induces rapid, clinically significant weight gain. We aimed to evaluate the effectiveness of a lifestyle and life skills intervention, delivered within 4 weeks of antipsychotic medication initiation, in attenuating weight gain in youth aged 14-25 years with first-episode psychosis (FEP). METHODS We undertook a prospective, controlled study in two early psychosis community services. Intervention participants (n = 16) received a 12-week individualized intervention delivered by specialist clinical staff (nurse, dietician and exercise physiologist) and youth peer wellness coaches, in addition to standard care. A comparison group was recruited from a similar service and received standard care (n = 12). RESULTS The intervention group experienced significantly less weight gain at 12 weeks compared to standard care (1.8 kg, 95% CI -0.4 to 2.8 vs. 7.8 kg, 4.8-10.7, P < 0.001). Thirteen per cent (2/16) of the intervention group experienced clinically significant weight gain (greater than 7% of baseline weight), while 75% (9/12) of the standard care group experienced this level of weight gain. Similar positive effects of the intervention were observed for waist circumference. CONCLUSIONS A lifestyle and life skills intervention delivered as part of standard care attenuated antipsychotic-induced weight gain in young people with FEP. The intervention was acceptable to the young people referred to the service. Such interventions may prevent the seeding of future disease risk and in the long-term help reduce the life expectancy gap for people living with serious mental illness.

Aerobic Exercise Improves Cognitive Functioning in People With Schizophrenia: A Systematic Review and Meta-Analysis

Abstract Cognitive deficits are pervasive among people with schizophrenia and treatment options are limited. There has been an increased interest in the neurocognitive benefits of exercise, but a comprehensive evaluation of studies to date is lacking. We therefore conducted a meta-analysis of all controlled trials investigating the cognitive outcomes of exercise interventions in schizophrenia. Studies were identified from a systematic search across major electronic databases from inception to April 2016. Meta-analyses were used to calculate pooled effect sizes (Hedges g) and 95% CIs. We identified 10 eligible trials with cognitive outcome data for 385 patients with schizophrenia. Exercise significantly improved global cognition (g = 0.33, 95% CI = 0.13–0.53, P = .001) with no statistical heterogeneity (I2 = 0%). The effect size in the 7 studies which were randomized controlled trials was g = 0.43 (P < .001). Meta-regression analyses indicated that greater amounts of exercise are associated with larger improvements in global cognition (β = .005, P = .065). Interventions which were supervised by physical activity professionals were also more effective (g = 0.47, P < .001). Exercise significantly improved the cognitive domains of working memory (g = 0.39, P = .024, N = 7, n = 282), social cognition (g = 0.71, P = .002, N = 3, n = 81), and attention/vigilance (g = 0.66, P = .005, N = 3, n = 104). Effects on processing speed, verbal memory, visual memory and reasoning and problem solving were not significant. This meta-analysis provides evidence that exercise can improve cognitive functioning among people with schizophrenia, particularly from interventions using higher dosages of exercise. Given the challenges in improving cognition, and the wider health benefits of exercise, a greater focus on providing supervised exercise to people with schizophrenia is needed.

Prevalence and predictors of treatment dropout from physical activity interventions in schizophrenia: a meta-analysis.

OBJECTIVE Physical activity interventions have been shown to improve the health of people with schizophrenia, yet treatment dropout poses an important challenge in this population, and rates vary substantially across studies. We conducted a meta-analysis to investigate the prevalence and predictors of treatment dropout in physical activity interventions in people with schizophrenia. METHOD We systematically searched major electronic databases from inception until August 2015. Randomized controlled trials of physical activity interventions in people with schizophrenia reporting dropout rates were included. Two independent authors conducted searches and extracted data. Random-effects meta-analysis and meta-regression analyses were conducted. RESULTS In 19 studies, 594 patients with schizophrenia assigned to exercise interventions were investigated (age=37.2 years, 67.5% male, range=37.5%-100%). Trim and fill adjusted treatment dropout rate was 26.7% [95% confidence interval (CI)=19.7%-35.0%], which is more than double than in nonactive control interventions (odds ratio=2.15, 95% CI=1.29-3.58, P=.003). In the multivariate regression, qualification of the professional delivering the intervention (β=-1.06, 95% CI=-1.77 to -0.35, P=.003) moderated treatment dropout rates, while continuous supervision of physical activity approached statistical significance (P=.05). CONCLUSIONS Qualified professionals (e.g., physical therapists/exercise physiologists) should prescribe supervised physical activity for people with schizophrenia to enhance adherence, improve psychiatric symptoms and reduce the onset and burden of cardiovascular disease.

Physical activity and sedentary behavior in people with major depressive disorder: A systematic review and meta-analysis

BACKGROUND Low levels of physical activity (PA) and sedentary behavior (SB) are independent risk factors for cardiovascular disease and premature mortality in people with major depressive disorder (MDD). AIMS Investigate levels of PA and SB and their predictors in people with MDD. METHODS Electronic databases were searched from inception till 04/2016 for articles measuring PA and SB with a self-report questionnaire (SRQ) or objective measure (e.g. accelerometer) in people with MDD. Random-effects meta-analyses and meta-regression analyses were conducted. RESULTS Twenty-four eligible studies were identified including 2901 people with MDD (78.4% female, mean age=54 years; range: 21-77 years). People with MDD spent 126.0min (95%CI=91.9-160.1) per day engaging in all types of PA and spent 8.5hours (95%CI=7.51-9.62) during their waking day being sedentary. Compared to controls, people with MDD spent less time in total PA (SMD=-0.25, 95%CI=-0.03 to 0.15) and moderate to vigorous PA (SMD=-0.30, 95%CI=-0.40 to 0.21) and engaged in higher levels of SB (SMD=0.09, 95%CI=0.01-0.18). The proportion of people with MDD not meeting the recommended PA guidelines was 67.8% (n=13 studies), which was higher in studies relying on objective versus self-report measures (85.7% v 62.1%, p=0.04). People with MDD were more likely than controls to not meeting the recommended PA guidelines (OR = 1.50, 95%CI = 1.10–2.10). LIMITATIONS Heterogeneity was evident in most analyses. CONCLUSIONS Adults with MDD engage in low levels of PA and high levels of SB. PA and SB are independent predictors of mortality, therefore, future lifestyle interventions targeting both the prevention of SB and adoption and maintenance of PA are warranted.